1. Field of the Invention
The present invention relates generally to the fields of molecular biology and microbiology. More particularly, it concerns the use of antimicrobial peptides for the inhibition of microbial growth.
2. Description of Related Art
The first antibiotics were used clinically in the 1940s and 1950s, and their use has been increasing significantly since this period. Although an invaluable advance, antibiotic and antimicrobial therapy suffers from several problems, particularly when strains of various bacteria appear that are resistant to antibiotics. Interestingly, bacteria resistant to streptomycin were isolated about a year after this antibiotic was introduced (Waksman, 1945).
The development of antibiotic resistance is a serious and life-threatening event of worldwide importance. For example, strains of Staphylococcus are known that are immune to all antibiotics except one (Travis, 1994). Such bacteria often cause fatal hospital infections. Among other drug resistant organisms are: pneumococci that cause pneumonia and meningitis; Cryptosporidium and E. coli that cause diarrhea; and enterococci that cause blood-stream, surgical wound and urinary tract infections (Berkelman et. al., 1994). The danger is further compounded by the fact that antibiotic and antimicrobial resistance may be spread vertically and horizontally by plasmids and transposons.
Davies (1986) described seven basic biochemical mechanisms for naturally-occurring antibiotic resistance: (1) alteration (inactivation) of the antibiotic; (2) alteration of the target site; (3) blockage in the transport of the antibiotic; (4) by-pass of the antibiotic sensitive-step (replacement); (5) increase in the level of the inhibited enzyme (titration of drug); (6) sparing the antibiotic-sensitive step by endogenous or exogenous product; and (7) production of a metabolite that antagonizes action of inhibitor.
Antimicrobial peptides have been isolated from plants, insects, fish, amphibia, birds, and mammals (Gallo, 1998; Ganz & Lehrer, 1998). Although previously considered an evolutionarily ancient system of immune protection with little relevance beyond minimal primary protection, recent developments have found that mammalian cells express these peptide antibiotics during inflammatory events such as wound repair, contact dermatitis and psoriasis (From Nilsson, 1999). These peptides are apparently a primary component of innate host protection against microbial pathogenesis functioning to create pores in the cytoplasmic membrane of microorganisms (Oren et al., 1998). Furthermore, antimicrobial peptides also act on animal cells by stimulating them to change behaviors such as syndecan expression, chemotaxis, and chloride secretion (Gallo, 1998). After contact with microorganisms, vertebrate skin, trachea and tongue epithelia are rich sources of peptide antibiotics, which may explain the unexpected resistance of these tissues to infection (Russell et al. 1996).
The present invention seeks to overcome these and other drawbacks inherent in the prior art by providing new compositions, combined compositions, methods and kits, for use in reducing resistance to antimicrobials and antibiotics and for treating infections.